Zika virus (ZIKV) is a mosquito-borne flavivirus that causes severe human disease, including Guillain-Barr syndrome and congenital brain abnormalities such as microcephaly. The ongoing ZIKV epidemic, which continues unabated, has resulted in over 1 million infections in 48 countries and territories in the Americas and was declared a Public Health Emergency of International Concern by the World Health Organization. There are currently no FDA-approved therapeutics or vaccines to combat this devastating pathogen. Further, efforts to develop an effective therapeutic are hampered by the near complete dearth of knowledge regarding ZIKV-host interactions that are critical for virus propagation and/or disease pathogenesis. ZIKV encodes a single open reading frame that is co- and post-translationally processed into 10 proteins. We will use a large-scale proteomics approach to define the sites of phosphorylation on each ZIKV protein and determine their importance for viral propagation. If successful, the proposed studies would significantly advance our basic understanding of ZIKV protein function and uncover candidate host kinase and phosphatase machinery that could be targeted for antiviral development.